Special Feature Volume Progression in Autosomal Dominant Polycystic Kidney Disease: The Major Factor Determining Clinical Outcomes

Autosomal dominant polycystic kidney disease (PKD) is a hereditary condition characterized by the progressive enlargement of innumerable renal cysts that contribute to life-altering morbidity early in the course of the disease. Evidence indicates that the rate of increase in kidney volume can be reliably measured by magnetic resonance or computed tomography imaging, thus providing objective means to judge the effectiveness of therapies that are targeted to the aberrant growth of renal tubules. It is now possible, therefore, to monitor the effectiveness of potential therapies on the signature abnormality in autosomal dominant PKD before irreversible damage has been done by the cysts. Evidence accumulated from human cross-sectional and longitudinal studies and longitudinal studies of PKDmodels in animals provide strong support for the view that reducing the rate of kidney volume enlargement will ameliorate the late-stage development of renal insufficiency. Clin J Am Soc Nephrol 1: 148–157, 2006. doi: 10.2215/CJN.00330705 I n this review, we propose a new paradigm for the evalu-ation of progression early in the course of chronic renaldiseases that lead to renal insufficiency. In current prac-tice, GFR is considered the gold standard for quantifying the rate of progression in all renal disorders. However, owing to the remarkable degree to which intact nephrons can compen-sate for the loss of functioning parenchyma, GFR measure-ments fail to disclose ominous changes in tissue function in th